Regulation of autologous cells and tissues Dr Glenn Smith Director, Biological Science Section Scientific Evaluation Branch Medicines Regulation Division, TGA ARCS Scientific Congress Canberra 2016 10-11 August 2016
Therapeutic Goods Administration (TGA) • A division of the Australian Government Department of Health • Regulates the safety, quality and efficacy of therapeutic goods in Australia • Regulates medicines, devices, biologicals and blood • Operates under cost recovery arrangements Regulation of autologous cells and tissues 1
Exemptions under the biologicals framework • Non-viable tissues of animal origin e.g. porcine heart valves • Fresh viable human organs for direct donor-to-host transplantation • Fresh viable human haematopoietic progenitor cells for direct donor-to-host transplantation (e.g. bone marrow cells, cord blood) • Reproductive tissue (e.g. sperm, eggs, embryos) that have not been processed in any way apart from freezing • Autologous tissue and cells – collected from a patient under the care of a medical practitioner , and – manufactured for therapeutic treatment of a single indication , and – in a single course of treatment of that patient by the same medical practitioner , or by a person under their supervision • Other Autologous uses are not exempt in Australia Regulation of autologous cells and tissues 2
What’s in & what’s out Not regulated by the Regulated, but not as Regulated as TGA biologicals biologicals Assisted reproductive Biological prescription Human stem cells technologies medicines (vaccines, plasma derivatives) (in vitro fertilisation) Tissue-based products (skin, bone, ocular, Fresh viable organs Animal tissue products cardiovascular) (xenotransplantation) Fresh haematopoietic Cell-based products progenitor cells (genetically modified, in vitro Labile blood and blood (bone marrow transplants) cell expansion/depletion) components Cells and tissues made by a Combined cell and tissue medical practitioner for a Haematopoietic progenitor products (collagen matrices for single patient under the care cells (non-fresh transplants) localised cell delivery) of that medical practitioner Regulation of autologous cells and tissues 3
Why have an Excluded Goods Order? • Some products have been declared not to be therapeutic goods and thus not regulated by TGA as a result of: • Government policy and to reflect Australian Health Ministers Advisory Council decisions – e.g. assisted reproductive therapy, fresh haematopoietic progenitor cells and organs for direct transplantation • Alternative regulatory pathways apply – Self-regulation for assisted reproductive therapy – NPAAC guidelines and NATA accreditation for haematopoietic stem cell programs – Organ and Tissue Authority requirements for organ transplantation – Medical practice Regulation of autologous cells and tissues 4
Medical practice and therapeutic product regulation intersect • Different regulatory frameworks oversee medical practice (Medical Board of Australia/ AHPRA) and therapeutic products (TGA), but the boundaries can overlap • Concerns may also arise under the Australian Consumer Law where consumers are misled or deceived into believing that certain treatments are safe or effective when that is not the case • Some autologous cell products are excluded from TGA regulation under the Therapeutic Goods (Excluded TGA Goods) Order 1 of 2011 under certain conditions Regulation of autologous cells and tissues 5
Excluded Goods Order No.1 of 2011 Goods that are not treated by the TGA as coming within the regulatory framework created by the Therapeutic Goods Act 1989 (the Act) and Regulations: o. fresh viable organs, or parts of human organs, for direct donor-to-host transplantation and used in accordance with applicable laws and standards p. fresh viable human haematopoietic progenitor cells for direct donor-to-host transplantation for the purpose of haematopoietic reconstitution r. reproductive tissue for use in assisted reproductive therapy Regulation of autologous cells and tissues 6
Excluded Goods Order No.1 of 2011 q. human tissue and cells that are: i. collected from a patient who is under the clinical care and treatment of a medical practitioner registered under a law of a State or an internal Territory and i. manufactured by that medical practitioner, or by a person or persons under the professional supervision of that medical practitioner, for therapeutic application in the treatment of a single indication and in a single course of treatment of that patient by the same medical practitioner, or by a person or persons under the professional supervision of the same medical practitioner Regulation of autologous cells and tissues 7
Excluded Goods Order Key considerations • Autologous cells and tissues only • Patient under the care of the same registered medical practitioner • Collection, ‘manufacture’ and application of cells or tissues under professional supervision of that medical practitioner • Single course of treatment and indication • Responsibility Regulation of autologous cells and tissues 8
Clinical procedures/treatments potentially within the current Item 4(q) exclusion Autologous • Skin grafts • Skull flaps • Vascular conduits • Pancreatic islet cells • Bone grafts • HPCs for reconstitution of blood after treatment for cancer • Blood components • Cosmetic/reconstructive procedures (bone, skin and fat transfers) • Autologous stem cells Regulation of autologous cells and tissues 9
Excluded Goods Order Other considerations • Standards relating to professional performance and advertising - regulated by the Australian Health Practitioner Regulation Agency • Professional obligations of medical practitioners to maintain satisfactory standards of practice • Whether the treatment being undertaken is necessary and safe and if efficacy is supported by credible clinical evidence • Provision of adequate information to patients to enable them to give informed consent to treatment • Regulation of advertising including under the provisions of the Competition and Consumer Act 2010 • Equipment and materials that are used for the manufacture of the product that may still be therapeutic goods subject to regulation by the TGA Regulation of autologous cells and tissues 10
Concerns with the current regulatory model • Lack of evidence to support the efficacy of autologous stem cells • Large sums of money being charged for unproven treatments • Safety of some stem cell products – either direct safety impacts or safety issues incidental to the therapy • Lack of mechanisms for reporting of adverse effects of the products • Inappropriate advertising of the products Stem cell clinics exploiting regulatory loop holes to sell Stem cell ‘tourists’ flock to Australia questionable treatments: experts • The Australian • ABC Online 2:00AM August 5, 2016 Untested stem cell treatments proliferate in Australia, study finds Unproven stem cell treatments multiply amid loophole The Guardian 5 August 2016 Medical Observer Regulation of autologous cells and tissues 11
Understanding of risks of cell therapies is limited • Can risk of infectious disease transmission ever be eliminated ? – Cells and tissues often cannot be sterilised fully – Donor screening – difficult to obtain complete history for deceased donors – Subjective nature of exclusion decisions – Evolving knowledge e.g. prions and degenerative neurological diseases • Many biologicals cannot be stopped once in a recipient’s body • Limited adverse event reporting because only some stem cell therapies are in formal clinical trials and adverse events can also be masked by poor prognosis of critically ill patients • Unforseen reactions have been reported – e.g. heart attack, severe thrombosis, encephalomyelitis, bone tissue Regulation of autologous cells and tissues 12
What are some other regulators doing? FDA • New guidances are more prescriptive about what defines ‘homologous use’ and ‘minimal manipulation’ • ‘Right to try’ movements also have momentum Europe • Only about five ‘advanced therapy medicinal products’ have been approved by EMA • ‘Hospital exemption system’ for some cell and tissue products rather than private clinics performing treatments Japan • ‘Provisional licensing’ system for cell therapies (SAKIGAKE initiative) • Where initial safety and manufacturing results positive; limited term commercial licensing to establish product efficacy and confirm safety 13 Regulation of autologous cells and tissues
Is current Australian regulation of autologous stem cell appropriate ? • Interpretation of ‘ minimally manipulated’ and ‘homologous use’ is relevant • USFDA takes a narrow view of ‘minimally manipulation’ and ‘homologous use’ for fat stem cells in Dec 2014 draft industry guidance documents • In Australia, a public consultation (Jan-Mar 2015) was held to seek input on five potential options for regulation of these cells as therapeutic goods • 80 submissions received 14 Regulation of autologous cells and tissues
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